{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:12:15Z","timestamp":1779970335053,"version":"3.53.1"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>MIT\u2010001 is a novel ferroptosis inhibitor that is a potent mitochondrial\u2010targeting antioxidant targeting various inflammatory diseases. Utilizing pharmacokinetic (PK) and safety data from previous clinical trials in healthy individuals with preclinical efficacy data from the animal disease models, we aimed to develop a population PK model for MIT\u2010001 to provide evidence for selecting optimal dosage in clinical trials with oral mucositis (OM) patients. The PK model was developed using data from three phase 1 clinical trials with NONMEM software. Covariate analysis included demographic characteristics and clinical laboratory tests. Models were validated using objective function value, goodness of fit plots, bootstrap analysis, and prediction\u2010corrected visual predictive check. PK profiles of MIT\u2010001 across various doses were simulated using the final population PK model. A three\u2010compartment model with linear elimination and first\u2010order absorption without a lag time best described the PK profile of MIT\u2010001. Weight and ALT were significant covariates for the peripheral compartment and clearance, respectively. The simulated PK profile showed that 97.4% of patients are expected to reach effective exposure after twice weekly 30 mg SC dose in 3 weeks. Furthermore, 93.6% of patients are expected to be within a tolerable range after 13 weeks of 80 mg SC dosing. A 30 to 80 mg twice weekly SC dose is expected to be both effective and tolerable for OM patients.<\/jats:p>","DOI":"10.1002\/jcph.70189","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T05:20:57Z","timestamp":1776316857000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic Analysis of MIT\u2010001, a Novel Ferroptosis Inhibitor, for Dose Optimization"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6584-9158","authenticated-orcid":false,"given":"Sungyeun","family":"Bae","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Republic of Korea"},{"name":"Department of Biomedical Sciences Seoul National University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8568-7320","authenticated-orcid":false,"given":"Eunwoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4010-0837","authenticated-orcid":false,"given":"Su\u2010jin","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Institute of Pharmaceutical Research College of Pharmacy, Wonkwang University  Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soonha","family":"Kim","sequence":"additional","affiliation":[{"name":"MitoImmune Therapeutics Inc.  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0921-7225","authenticated-orcid":false,"given":"Kyung\u2010Sang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Republic of Korea"},{"name":"Department of Biomedical Sciences Seoul National University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-9194","authenticated-orcid":false,"given":"SeungHwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2010.184"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdr391"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2009.08.006"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40496\u2010015\u20100069\u20104"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1534735404270335"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8091105"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.117.09405"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13213"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2020.08.011"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.S541415"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385\u2010019\u20100132\u2010x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.06.008"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2014.110"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1274"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.649"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.70021"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.6190"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.6146"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70189","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70189","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T11:54:50Z","timestamp":1779969290000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/jcph.70189"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70189","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70189"}}